The studies, focusing on sexual differentiation of the song system in zebra finches, will elucidate genes and their products important for nervous system, muscle and behavioral development. Only males sing, and the brain areas and muscles that control song are larger than in females. In many vertebrates, development of these types of dimorphisms is regulated by gonadal steroids. In zebra finches, differentiation can be altered with estrogen treatment, but recent data suggest that the forebrain song control regions differentiate independent of gonadal secretions. Therefore, a screen will be conducted for genes expressed in a sexually dimorphic pattern in the telencephalon during development of morphology and singing behavior. Then, genes/proteins regulating cytoarchitecture and/or specific functions (e.g., learning) will be investigated in more detail. Using this strategy, female-specific transcripts for neurocalcin were discovered. Experiments will clarify their role and that of calcium regulation in neural development. Other studies target the role of the estrogen-sensitive protein, brain derived neurotrophic factor (BDNF) in development of the song control nuclei and regions involved in song perception. These studies will clarify the importance of learning and the brain regions that are active during song perception in females (detailed information is already available for males), and will then test the hypothesis that BDNF modulates development of these telencephalic structures and song-related functions in both sexes. Finally, it will be determined whether mechanisms regulating development in the forebrain apply to the motor nucleus and vocal organ muscles, and whether sexual differentiation at this level is normally mediated by gonadal steroids, similar to other dimorphic model systems. The candidate for this Independent Scientist Award is an associate professor at Michigan State University, and her teaching load and service obligations are substantial. The award would provide her time to (1) enhance her training in molecular techniques (those proposed in collaboration with other scientists, and new ones useful for future experiments); (2) broaden her anatomical expertise; (3) contribute to the proposed studies more directly, which will increase the rate of progress; and (4) enhance collaborations and visibility of her growing neuroendocrine group, as well as training of students and postdocs, by establishing a seminar series with leaders in her field.